Ketals 3-keto esters

Hydrogenation was carried out at O to minimize decarboxylation of the saturated 3-keto acid product 18. Mannich reaction proceeded with in situ decarboxylation to afford a-methylene ketone 19, which on Michael reaction with ketal 3 keto ester 20 -" yielded adduct 21. Saponification, B ring closure, and decarboxylation then led to ketalenone 23 in high yield, which was converted into ( + )-19-nortestosterone 24 and thence to ( + )-19-norandrostenedione 25 in 50% yield from 18 or 27% overall yield from 12. However, ketal hydrolysis, A ring closure, oxidation at C-17, and isomerization by the Roussel procedure (acetyl bromide-acetic anhydride in methylene chloride at 20°) should yield (-f )-estrone 26 efficiently. 

The signal molecule, 30,C6-HSL and number of its analogues, with variations in the acyl chain and the hetero-ring, have been prepared [15,56,57] to investigate the mechanism of induction of carbapenem and luminescence in Erwinia carotovora and V.fischeri respectively. Essentially, the acylation of l-HSL with 3-oxoalkanoic acid by the same method as outlined for the preparation of AT-acyl-L-HSL delivers the desired derivatives. However, as the p-keto acids are thermally labile, these were prepared from the corresponding p-keto ester after the initial protection of the p-keto function as ethylene glycol ketal (route a, Scheme 6). 

Another way of avoiding reduction of the keto group in a keto ester is protection by acetalization. Ketals are evidently not reduced by lithium... 

The second procedure, Part B, Illustrates an easy synthesis of y-keto esters by "reductive succlnoylation" of a ketal function.5 It is useful not only for the preparation of keto esters, but also as a four-carbon chain-elongation reaction starting from ketones. The reaction is applicable to a diverse range of ketals as shown in Table II. The enol silyl ether... 

Cyclopropenone ketals can undergo a similar [3 -I- 2] cycloaddition with aldehydes or ketones to provide butenolide ortho esters, which in turn can be converted into butenolides, furanes, or y-keto esters. ... 

Methyl cyanoformate. Zinc, y KETO esters Cyclopropenone 1,3-propane diyl ketal. 1-Ethoxy-1-trimelhylsilyloxycy-clopropane. Methyl a-chloro-a-phenyl-thioacclate. Titanium(IV) chloride. 

Acetals and ketals having a second junctional group ate made by these procedures. For example, acrolein reacts with ethyl orthoformate in alcohol solution with ammonium nitrate as catalyst to give acrolein diethyl acetal (73%). On the other hand, it reacts with ethyl ortho silicate with anhydrous hydrogen chloride as catalyst to furnish (i-ethoxypropionaldehyde diethyl acetal (76%). p-Bromoacetophenone and ethyl orthoformate give the corresponding ketal in 65% yield. p-Methoxy- and m-amino-benzaldehyde diethyl acetals are made in a similar way in 96% and 85% yields, respectively. a-Keto esters like ethyl a-keto-n-butytate and ethyl a-keto-tr-valetate are converted to their diethyl ketals in excellent yields by the action of orthoformic ester in ethanol-hydrochloric acid solution. If the reaction is carried out in the presence of ethylene glycol instead of ethanol and, in addition, the volatile products are removed by distillation, then the ethylene ketal is formed in almost quantitative yield (cf. method 133). 

Tishchenko and coworkers obtained dihydrofuran derivatives when 2-benzoyl-1,1-dichlorocyclopropane (102) was treated with alkoxides (Scheme 40) . Product (107) is highly reminiscent of butenolide (70) obtained by the addition of chloromethoxycarbene to acrolein as discussed earlier (Scheme 29) and may result from ring-opening of cyclopropanone ketal (104). Perhaps a more likely mechanism involves addition of alkoxide to intermediate 103 followed by cyclization 106 - 107. When treated with thiophenoxide, 102 gave cyclopropanone dithioketal (108). A similar result has been obtained by Ban well (Scheme 41) . Treatment of 109 with thiophenoxide gave dithioketal 110 in 98 % yield. In contrast to the results of Tishchenko, however, keto ester products (112) were obtained from 2,2-dichloro-l-acylcyclopropanes (111) and alkoxides (Scheme 42) ... 

Scheme 7-116 From chiral cyclopropanonc ketals to ge/n-disubstituted keto-esters or -diesters.

After conversion to 19 (70% yield) via Nef reaction and ketalization, selective modification of the terminal olefin by reaction with LAH-TiCl4, quenching with I2, and displacement of the resulting terminal halogen with ethyl acetoacetate anion afforded 20 in 48% overall yield. Deacetylation with sodium ethoxide followed by deketalization under acidic conditions produced an 88% yield of keto ester 21. Seco acid 6 was then obtained (in 29% yield from 18) after reduction of the ketone and ester hydrolysis. Clearly, the significance of this... 

P-ffeto esters tt-methylene ketones The anhydride (1) undergoes Diels-Alder reactions with dienes at 0-80° to give only endo-adducts usually only one of the two possible cnrfo-adducts is formed. The double bond in the adducts can be reduced without desulfurization with H2 and PdfOH) on carbon. The adducts are convertible by oxidative decarboxylation with NCS (6, 116-117) to the ketal and/or the enol thioether of a j3-keto ester, both of which are hydrolyzable to... 

Diacids.—Cyclic /3-keto-sulphides, which are easily prepared from the parent ketone, can be oxidized to the acetates (7), which on further oxidation with alkaline hydrogen peroxide undergo ring opening to aw-diacids (Scheme 4). Similar treatment of linear carboxylic acid esters, but using iodine in methanol in the final step, leads to a a-keto-ester ketals (8). 

---